Sleep benefit in Parkinson's disease: time to revive an enigma?

J Parkinsons Dis. 2012;2(2):167-70. doi: 10.3233/JPD-2012-12087.

van Gilst MM, Louter M, Baumann CR, Bloem BR, Overeem S.

Source

Department of Neurology, Donders Institute for Brain, Cognition and Behavior, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands.

Abstract

Some patients with Parkinson's disease (PD) reportedly experience 'sleep benefit': an improved motor functioning upon awaking in the morning. In this questionnaire study, 114 out of 243 consecutive outpatients with PD (46.9%) subjectively experienced sleep benefit. Among those patients that regularly took an afternoon nap, 33.7% experienced sleep benefit after the nap as well. Between patients with and without sleep benefit, there were no differences in demographic or clinical variables, including age, disease duration, dopaminergic treatment, and nocturnal sleep quality. Sleep benefit remains an intriguing but elusive phenomenon, which deserves renewed attention and further research.

REM sleep behavior disorder and motor dysfunction in Parkinson's disease - A longitudinal study

Parkinsonism Relat Disord. 2013 Aug 5. pii: S1353-8020(13)00271-X. doi: 10.1016/j.parkreldis.2013.07.017. [Epub ahead of print]

Bugalho P, Viana-Baptista M.

Source

Neurology Department Hospital de Egas Moniz (CHLO), Lisboa, Portugal; Departamento de Neurologia, CEDOC, Faculdade de Ciências Médicas, Universidade Nova de Lisboa, 1169-056 Lisbon, Portugal. 

Abstract

OBJECTIVES:

Longitudinal assessment of a Parkinson's disease (PD) cohort, to investigate the evolution or REM sleep behavior symptoms (RBD) over time and to test the relation between RBD at onset and motor dysfunction progression.

METHODS:

An early stage PD cohort (n = 61) was assessed at two time points, separated by a two years interval. Diagnostic criteria for RBD were: violent behavior during sleep and body movements or vocalization indicative of dream enacting and at least six affirmative answers in the REM sleep behavior disorder screening questionnaire. Motor function assessment was performed with the Unified Parkinson's Disease Scale part II and III (total and partial scores for tremor, bradykinesia, rigidity, gait/postural instability and dysarthria).

RESULTS:

25 Patients had RBD at baseline, vs. 35 at follow-up. Three RBD changed to non-RBD at follow-up, while 10 non-RBD patients developed RBD at follow-up (annual incidence of 12.5%). RBD and non-RBD patients did not differ significantly at baseline or follow-up. The presence of RBD at baseline was significantly related to an increase in UPDRS total and bradykinesia scores over time.

DISCUSSION:

RBD symptoms can vary over time and have a tendency to increase during the early stages of disease. The presence of RBD symptoms could be a risk factor for motor function deterioration and particularly for bradykinesia worsening.

Dementia with Lewy bodies: early diagnostic challenges

Psychogeriatrics. 2013 Jun;13(2):128-38. doi: 10.1111/psyg.12005.

Fujishiro H, Iseki E, Nakamura S, Kasanuki K, Chiba Y, Ota K, Murayama N, Sato K.

Source

PET/CT Dementia Research Center, Juntendo Tokyo Koto Geriatric Medical Center; Department of Psychiatry, Juntendo University School of Medicine, Tokyo, Japan.

Abstract

Dementia with Lewy bodies (DLB) is defined pathologically as neurodegeneration associated with Lewy bodies (LB). LB-related symptoms, including olfactory dysfunction, dysautonomia, and mood and sleep disorders, are increasingly recognized as clinical signs that enable the early detection of DLB, because these symptoms often antedate dementia by years or even decades. It remains unknown if the clinical history of LB-related symptoms is sufficient for the prodromal state of DLB to be suspected in memory clinics. We retrospectively investigated the clinical courses, including olfactory dysfunction, dysautonomia, depression, and rapid eye movement sleep behaviour disorder, of 90 patients with probable DLB. The timing of LB-related symptoms that preceded or followed relative to the onset of memory loss was calculated. LB-related symptoms were present in 79 of 90 patients (87.8%) with probable DLB before or at the time of memory loss onset. These symptoms preceded the onset of memory loss between 1.2 and 9.3 years. We also report on four non-demented patients with a clinical history of LB-related symptoms in our memory clinic. All four patients showed reduced cardiac [(123) I]-metaiodobenzylguanidine levels. Moreover, [(18) F]fluoro-D-glucose positron emission tomography scans revealed glucose hypometabolism in the occipital cortex in two patients. One patient converted to probable DLB with the development of parkinsonism 2 years after major depression was diagnosed. Based on a clinical history of LB-related symptoms, we propose a conceptual framework to identify these symptomatic but non-demented individuals that led us to suspect the underlying pathophysiology of Lewy body disease. Further prospective study is warranted to determine the clinical significance of LB-related symptoms in non-demented patients.

Population-specific frequencies for LRRK2 susceptibility variants in the genetic epidemiology of Parkinson's disease (GEO-PD) consortium

Mov Disord. 2013 Aug 2. doi: 10.1002/mds.25600. [Epub ahead of print]

Heckman MG, Soto-Ortolaza AI, Aasly JO, Abahuni N, Annesi G, Bacon JA, Bardien S, Bozi M, Brice A, Brighina L, Carr J, Chartier-Harlin MC, Dardiotis E, Dickson DW, Diehl NN, Elbaz A, Ferrarese C, Fiske B, Gibson JM, Gibson R, Hadjigeorgiou GM, Hattori N, Ioannidis JP, Boczarska-Jedynak M, Jasinska-Myga B, Jeon BS, Kim YJ, Klein C, Kruger R, Kyratzi E, Lesage S, Lin CH, Lynch T, Maraganore DM, Mellick GD, Mutez E, Nilsson C, Opala G, Park SS, Petrucci S, Puschmann A, Quattrone A, Sharma M, Silburn PA, Sohn YH, Stefanis L, Tadic V, Theuns J, Tomiyama H, Uitti RJ, Valente EM, Van Broeckhoven C, van de Loo S, Vassilatis DK, Vilariño-Güell C, White LR, Wirdefeldt K, Wszolek ZK, Wu RM, Hentati F, Farrer MJ, Ross OA; on behalf of the Genetic Epidemiology of Parkinson's Disease (GEO-PD) Consortium.

Source

Biostatistics Unit, Mayo Clinic, Jacksonville, Florida, USA.

Abstract

BACKGROUND:

Variants within the leucine-rich repeat kinase 2 gene are recognized as the most frequent genetic cause of Parkinson's disease. Leucine-rich repeat kinase 2 variation related to disease susceptibility displays many features that reflect the nature of complex, late-onset sporadic disorders like Parkinson's disease.

METHODS:

The Genetic Epidemiology of Parkinson's Disease Consortium recently performed the largest genetic association study for variants in the leucine-rich repeat kinase 2 gene across 23 different sites in 15 countries.

RESULTS:

Herein, we detail the allele frequencies for the novel risk factors (p.A419V and p.M1646T) and the protective haplotype (p.N551K-R1398H-K1423K) nominated in the original publication. Simple population allele frequencies not only can provide insight into the clinical relevance of specific variants but also can help genetically define patient groups.

CONCLUSIONS:

Establishing individual patient-based genomic susceptibility profiles that incorporate both risk factors and protective factors will determine future diagnostic and treatment strategies.

Impulse control disorders in Parkinson's disease: decreased striatal dopamine transporter levels

J Neurol Neurosurg Psychiatry. 2013 Jul 30. doi: 10.1136/jnnp-2013-305395. [Epub ahead of print]

Voon V, Rizos A, Chakravartty R, Mulholland N, Robinson S, Howell NA, Harrison N, Vivian G, Ray Chaudhuri K.

Source

Department of Psychiatry, University of Cambridge, , Cambridge, UK.

Abstract

OBJECTIVE:

Impulse control disorders are commonly associated with dopaminergic therapy in Parkinson's disease (PD). PD patients with impulse control disorders demonstrate enhanced dopamine release to conditioned cues and a gambling task on [11C]raclopride positron emission tomography (PET) imaging and enhanced ventral striatal activity to reward on functional MRI. We compared PD patients with impulse control disorders and age-matched and gender-matched controls without impulse control disorders using [123I]FP-CIT (2β-carbomethoxy-3β-(4-iodophenyl)tropane) single photon emission computed tomography (SPECT), to assess striatal dopamine transporter (DAT) density.

METHODS:

The [123I]FP-CIT binding data in the striatum were compared between 15 PD patients with and 15 without impulse control disorders using independent t tests.

RESULTS:

Those with impulse control disorders showed significantly lower DAT binding in the right striatum with a trend in the left (right: F(1,24)=5.93, p=0.02; left: F(1,24)=3.75, p=0.07) compared to controls.

CONCLUSIONS:

Our findings suggest that greater dopaminergic striatal activity in PD patients with impulse control disorders may be partly related to decreased uptake and clearance of dopamine from the synaptic cleft. Whether these findings are related to state or trait effects is not known. These findings dovetail with reports of lower DAT levels secondary to the effects of methamphetamine and alcohol. Although any regulation of DAT by antiparkinsonian medication appears to be modest, PD patients with impulse control disorders may be differentially sensitive to regulatory mechanisms of DAT expression by dopaminergic medications.

Poor self-awareness of levodopa-induced dyskinesias in Parkinson's disease: Clinical features and mechanisms

Parkinsonism Relat Disord. 2013 Jul 23. pii: S1353-8020(13)00241-1. doi: 10.1016/j.parkreldis.2013.07.002. [Epub ahead of print]

Pietracupa S, Fasano A, Fabbrini G, Sarchioto M, Bloise M, Latorre A, Altieri M, Bologna M, Berardelli A.

Source

Department of Neurology and Psychiatry, Sapienza University of Rome, Italy.

Abstract

OBJECTIVES:

To study the factors and possible mechanisms associated with decreased self-awareness of levodopa-induced dyskinesias (LIDs) in patients with Parkinson's disease (PD).

METHODS:

We enrolled 30 PD patients with LIDs. Patients were video-recorded in an "on" phase while experiencing LIDs. LIDs were objectively rated by means of the Unified Dyskinesias Rating Scale (UDyRS) by two movement disorders specialists while examining the patients. Patients were asked to rate the body site and the severity of their LIDs according to the 5-point UDyRS. Patients then rated their own LIDs while watching the video recording of themselves. Lastly, the patients rated the LIDs of other reference PD patients on a video recording. The same reference video recordings were shown to 15 healthy individuals matched for age, gender and education.

RESULTS:

Seven of the 30 PD patients investigated were subjectively unaware of the presence of their LIDs. The majority of patients, however, recognized their LIDs when watching video recording of themselves. Patients displayed a specific poor self-awareness of trunk LIDs, in both the subjective evaluation and in the video recording-based subjective evaluation. By contrast PD patients correctly recognized LIDs in video recordings of reference PD patients. Poor self-awareness correlated with predominance of motor symptoms on the left body side.

CONCLUSIONS:

Poor self-awareness of LIDs is present in a proportion of PD patients as a form of anosognosia. The poor self-awareness of LIDs in the trunk is likely to be due to a complex interplay involving both anosognosic mechanisms and deficits in proprioceptive axial kinesthesia.

"PSP is one of the atypical Parkinsonian disorders..."

"... It is often confused with Parkinson's disease but has some key features which make it different. Like people with Parkinson's disease, those with PSP are in desperate need of treatments that can help ease their suffering and ultimately offer a cure."

"This is an short film about what life is like for patients with PSP and those that care for them."

- Alastair Noyce

Risk factors for dementia with Lewy bodies: A case-control study

Neurology. 2013 Jul 26. [Epub ahead of print]

Boot BP, Orr CF, Ahlskog JE, Ferman TJ, Roberts R, Pankratz VS, Dickson DW, Parisi J, Aakre JA, Geda YE, Knopman DS, Petersen RC, Boeve BF.

Source

From the Departments of Neurology (B.P.B, C.F.O., J.E.A., Y.E.G., D.S.K., R.C.P., B.F.B.), Psychiatry and Psychology (T.J.F., Y.E.G.), Health Sciences Research (R.R., V.S.P., J.A.A., Y.E.G.), Anatomic Pathology (D.W.D.), and Robert H. and Clarice Smith and Abigail Van Buren Alzheimer's Disease Research Program of the Mayo Foundation (B.P.B., C.F.O., Y.E.G., D.S.K., R.C.P., B.F.B.), Mayo Clinic College of Medicine, Rochester MN, Scottsdale, AZ, and Jacksonville FL. B.P.B. is currently affiliated with the Neurology Department, Brigham and Women's Hospital, Boston, MA. C.F.O. is currently affiliated with Macquarie Neurology, Macquarie University Hospital, NSW, Australia.

Abstract

OBJECTIVE:

To determine the risk factors associated with dementia with Lewy bodies (DLB).

METHODS:

We identified 147 subjects with DLB and sampled 2 sex- and age-matched cognitively normal control subjects for each case. We also identified an unmatched comparison group of 236 subjects with Alzheimer disease (AD). We evaluated 19 candidate risk factors in the study cohort.

RESULTS:

Compared with controls, subjects with DLB were more likely to have a history of anxiety (odds ratio; 95% confidence interval) (7.4; 3.5-16; p < 0.0001), depression (6.0; 3.7-9.5; p < 0.0001), stroke (2.8; 1.3-6.3; p = 0.01), a family history of Parkinson disease (PD) (4.6; 2.5-8.6; p < 0.0001), and carry APOE ε4 alleles (2.2; 1.5-3.3; p < 0.0001), but less likely to have had cancer (0.44; 0.27-0.70; p = 0.0006) or use caffeine (0.29; 0.14-0.57; p < 0.0001) with a similar trend for alcohol (0.65; 0.42-1.0; p = 0.0501). Compared with subjects with AD, subjects with DLB were younger (72.5 vs 74.9 years, p = 0.021) and more likely to be male (odds ratio; 95% confidence interval) (5.3; 3.3-8.5; p < 0.0001), have a history of depression (4.3; 2.4-7.5; p < 0.0001), be more educated (2.5; 1.1-5.6; p = 0.031), have a positive family history of PD (5.0; 2.4-10; p < 0.0001), have no APOE ε4 alleles (0.61; 0.40-0.93; p = 0.02), and to have had an oophorectomy before age 45 years (7.6; 1.5-39; p = 0.015).

CONCLUSION:

DLB risk factors are an amalgam of those for AD and PD. Smoking and education, which have opposing risk effects on AD and PD, are not risk factors for DLB; however, depression and low caffeine intake, both risk factors for AD and PD, increase risk of DLB more strongly than in either.

Epidemiology of dementia with Lewy bodies--the Alzheimer-Parkinson overlap

Neurology. 2013 Jul 26. [Epub ahead of print]

Postuma RB.

Abstract

Dementia with Lewy bodies (DLB) is viewed by many as a condition that combines features of Alzheimer disease (AD) and Parkinson disease (PD). Autopsy in DLB discloses both amyloid and synuclein deposition, and the relative degree of each may determine the clinical phenotype.1 Despite being the second most common form of dementia, risk factors of DLB have never been systematically studied. The current report by Boot et al.2 therefore represents a considerable advance. Relying on data from 3 separate cohorts, the authors found that the risk factor profile of DLB appeared to combine aspects of AD and PD. Known risk factors for PD, such as nonuse of caffeine, anxiety, depression, and family history of PD were present in DLB. Similarly, AD risk factors such as APOE status, depression, and stroke were also present in DLB. Smoking, a protective factor for PD and a risk factor for AD, was not associated with DLB, perhaps suggesting that the risk factors "canceled out." However, when risk factors were common between conditions (depression and caffeine use), the relationship in DLB appeared to be stronger than for AD or PD individually, suggesting additive risks. Although the risk factors were not always comprehensively assessed and diagnosis was clinical in the majority of cases (albeit with broadly similar results in the subgroup with autopsy confirmation), the study is well-designed and comprehensively analyzed. In addition to providing for the first time a broad picture of risk factors for DLB, the study reinforces the close interactions among DLB, PD, and AD, and points to the potential importance of multiple interacting pathologies in determining clinical disease.

Surgical treatment of Parkinson disease: past, present, and future

Neurol Clin. 2013 Aug;31(3):799-808. doi: 10.1016/j.ncl.2013.03.007. Epub 2013 Apr 4.

Duker AP, Espay AJ.

Source

Department of Neurology and Rehabilitation Medicine, James J. and Joan A. Gardner Center for Parkinson's Disease and Movement Disorders, University of Cincinnati Neuroscience Institute, University of Cincinnati, 260 Stetson Street, Suite 2300, Cincinnati, OH 45267-0525, USA.

Abstract

Advances in functional neurosurgery have expanded the treatment of Parkinson disease (PD) to targeted electrical stimulation of specific nodes in the basal ganglia circuitry. Deep brain stimulation (DBS), applied to selected patients and difficult-to-manage motor fluctuations, yields substantial reductions in off time and dyskinesia. Emerging concepts in DBS include examination of new targets, such as the potential efficacy of pedunculopontine nucleus stimulation for treatment of freezing and falls, the use of pathologic oscillations in the beta band to construct an adaptive "closed-loop" DBS, and new technologies, including segmented electrodes to steer current toward specific neural populations.

Cognitive impairment and PD patients' capacity to consent to research

Neurology. 2013 Jul 26. [Epub ahead of print]

Karlawish J, Cary M, Moelter ST, Siderowf A, Sullo E, Xie S, Weintraub D.

Source

From the University of Pennsylvania (J.K., M.C., E.S., S.X., D.W.), Department of Medicine (J.K., E.S.), Department of Medical Ethics and Health Policy (J.K.), Alzheimer's Disease Center (J.K.), Neurodegenerative Disease Ethics and Policy Program (J.K., E.S.), Leonard Davis Institute of Health Economics (J.K.), Center for Clinical Epidemiology and Biostatistics (M.C., S.X.), Department of Psychiatry (D.W.), Parkinson's Disease (D.W.) and Mental Illness (D.W.) Research, Education and Clinical Centers; University of the Sciences in Philadelphia (S.T.M.); and Avid Radiopharmaceuticals (A.S.), Philadelphia, PA.

Abstract

OBJECTIVE:

To examine how cognitive impairment affects Parkinson disease (PD) patients' research consent capacity.

METHODS:

A cross-sectional study of 90 patients with PD, divided using Mattis Dementia Rating Scale-2 scores into 3 groups of 30 (normal, borderline, and impaired), and 30 neurologically normal older adults completed 2 capacity interviews (an early-phase randomized and controlled drug trial and a sham-controlled surgical implantation of genetic tissue) using the MacArthur Competence Assessment Tool for Clinical Research. Expert clinicians used the interviews to classify the patients as either capable or not capable of providing their own informed consent. These judgments were compared with performance on the Montreal Cognitive Assessment (MoCA) and the Mini-Mental State Examination (MMSE).

RESULTS:

Cognitively normal PD patients typically scored well on the capacity measures. In contrast, patients with impaired cognition were not capable of providing their own informed consent: 17% (5/30) on the drug trial and 3% (1/30) on the surgery trial were judged capable. Patients with borderline impairment showed adequate performance on measures of appreciation and reasoning, but impaired performance on understanding the drug trial compared with normal controls and normal PD patients, and on understanding the surgery trial compared with normal controls. Sixty-seven percent (20/30) on the drug trial and 57% (17/30) on the surgery trial were judged capable of consent. Receiver operating characteristic analyses showed that the MMSE and MoCA could detect the likelihood of impaired capacity, with the MoCA demonstrating greater sensitivity.

CONCLUSIONS:

PD patients with borderline cognitive impairment have impairments in their decisional capacity. The MoCA may be useful to identify the patients at risk of impaired capacity.